The traditional structure-function paradigm has provided significant insights for well-folded proteins in which structures can be easily and rapidly revealed by X-ray crystallography beamlines and NMR. However approximately one third of the human proteome are comprised of intrinsically disordered proteins and regions that do not adopt a dominant well-folded structure, and therefore remain ?unseen? by traditional structural biology methods. Current experimental and computational approaches to structural descriptions of disordered proteins, while often valuable, still lack predictive power, particularly for dynamic complexes of IDPs, as well as lack of insight into the relationships between IDP structural ensembles and function. This is because IDPs require an unprecedented level of integration of multiple and complementary solution-based experiments, state-of-the art molecular simulations to provide realistic and relevant models for IDP ensembles, selection of the best ensembles via Bayesian probabilistic approaches given the underdetermined nature of the problem, and comprehensive analysis to connect observed dynamic structure with function relevant to the biological questions being addressed. We propose the development of IDP Calculator, which will (1) quantify the usefulness and information content of a large set of experimental data types such as chemical shifts, scalar couplings, RDCs, NOEs, PREs, and FRET/FCS; (2) use a variety of advanced atomistic and coarse-grained models and sampling methods for generating candidate ensembles of IDP and their complexes; (3) apply new Bayesian models for IDP ensemble selection that both evaluates and optimizes the candidate ensembles with the best experimental data types; and (4) create a software suite that will integrate these methods along with tools to perform correlative analysis of structural, sequence, binding and other functional data on a wide range of IDP problems. The computational approaches to be developed will advance the characterization of structural ensembles for proteins with intrinsic disorder, not only for the free monomer, but with emphasis on IDP complexes. We will develop and validate our approaches on a wide range of systems: the dynamic complex of Sic1:Cdc4 that regulates the yeast cell cycle, complexes formed between protein phosphatase 1 and its disordered regulators that control diverse cellular processes, and monomeric and phase-separated FUS and TDP-43 IDPs important for understanding the dynamic intermolecular contacts leading to biological phase separation and ALS-associated aggregation.